Santaris Pharma

Santaris developed drugs based on Locked Nucleic Acids (LNA) to facilitate the identification and design of potential drug candidates. LNAs are modified RNA molecules, featuring an oxymethylene bridge between the 2’ oxygen and 4’ carbon in the ribose ring. This structural alteration forms a bi-cyclic configuration that enhances the stability and binding affinity of LNAs to their complementary RNA sequences.

LNA oligonucleotides were engineered by Santaris as antisense therapeutic agents, designed to complement specific mRNA and microRNA sequences. This interaction leads to the formation of double-stranded RNA, preventing translation. Notably, LNA oligonucleotides are shorter than other antisense drugs, granting them greater target affinity and potency compared to regular RNA oligonucleotides.

One of the distinctive qualities of LNA drugs is their resistance to endonuclease activity, which contributes to their durability. Moreover, LNA drugs possess several advantageous attributes: they can be administered without the need for complex drug delivery methods, their production is scalable and cost-effective, they are well-tolerated, and there exists potential for oral administration. These factors collectively define LNA-based drugs as innovative therapeutic agents.[7] [4] [3]

Santaris partnered with several pharmaceutical companies that wanted to develop LNA oligonucleotides for mRNA and microRNA targets. Pfizer and Santaris entered a collaboration pact in 2009, which was expanded in 2011.[13] It also partnership with Enzon for cancer drug targets, [9] Shire for lead candidates of five rare, undisclosed genetic disorders,[9] miRagen to develop treatments targeting microRNAs associated with cardiovascular disease, and GlasoSmithKline for four viral disease programs and clinical trials.[14]

Santaris employees have co-authored articles published in Nature (2008),[15] and Science (2009).[16] These have outlined the results of experiments using LNA oligonucleotides to down-regulate the expression of endogenous microRNAs in primates.

• 2003: Santaris was founded through a merger of Cureon and Pantheco.[3]
• 2004: Began cancer drug development – LNA-based drugs SPC3042 targeting Survivin and SPC2968 targeting HIF-1alpha.[7]
• 2005: Began a miRNA research and drug development program.[7]
• 2006: Partnership with Enzon for cancer therapeutics.[9]
• 2007: Commencement of preclinical development of SPC3649, a microRNA-targeted drug for the treatment of Hepatitis C.[3] Established commercial partnership with GlaxoSmithKline for global research and development and of up four programs in viral diseases.[17] Enzon files IND and completes two Phase I/II US studies of advanced cancer research with EZN-2968.[9]
• 2008: Biotech grant from Danish Advanced Technology for microRNA antagonist research for 45m DKK.[18] Santaris Pharma named one of the “Fierce 15” Biotech Companies of 2008 by FierceBiotech.[1] Advanced to Phase 1 clinical trials for the treatment of HCV using a microRNA-targeted drug, SPC3649.[7] Study published in Nature that shows LNA-based drugs targeting microRNAs capacity in non-human primates.[15]
• 2009: Establishment of a branch in San Diego, California, United States of America.[2] Formed collaboration with Shire to develop RNA-based medicines for the treatment of rare genetic disorders.[9] Advanced the 4955 into drug development, which is a compound that targets Apolipoprotein B and could decrease and manage high cholesterol into drug development.[7] Publication in Science showing how the breakthrough microRNA-targeted therapy SPC3649 is a promising new treatment for Hepatitis C.[16] Wyeth Pharmaceuticals and Santaris Pharma announce their partnership to develop RNA-targeted medicines.[19]
• 2010: Santaris Pharma A/S and miRagen Therapeutics form an alliance to develop microRNA-targeted medicines for the treatment of cardiovascular disease.[14] Advanced SPC5001, which targets PCSK9, into drug development for the treatment of high cholesterol.[7] Received the Red Herring Top 100 Europe Award.[20]
• 2011: Obtained license from Mass General Hospital for intellectual property related to miR-33 regulations for cardiovascular disorder treatment.[21] Expanded collaborations with Pfizer Inc. directed on development of RNA-targeted medicines.[22] Santaris made medical history with their advancement of miravirsen to Phase II trials, which is the first microRNA-targeted drug to enter clinical trials, and aims to treat patients infected with Hepatitis C.[23]
• 2013: Santaris Pharma A/S and Bristol-Myers Squibb form an alliance to develop lead candidates against a limited number of targets
• 2013: Santaris Pharma A/S and RaNa form an alliance to develop lead candidates against <10 of RaNA’s proprietary RNA targets for the treatment of human diseases
• 2014: Santaris Pharma A/S was acquired by Roche and renamed the Roche Innovation Center Copenhagen.

• 2008: Fierce 15 by Fierce Biotechnology [1]
• 2010: Red Herring Top 100 Europe Award [20]
• 2011: Finalist for 2011 Scrip Awards in the "Clinical Research Team of the Year" category.[24]

• Santaris Pharma A/S vs. Exiqon A/S

Exiqon brought Santaris to court to obtain more rights of LNA technology in 2010. On Friday, October 7, 2011, all the allegations initiated by Exiqon against Santaris were dismissed by the arbitration court. The ruling confirmed that Santaris held exclusive worldwide rights to manufacture, have manufactured, and sell products that comprise LNA as active ingredients for studies performed to develop LNA-based drugs for marketing approval.[25]

• Santaris Pharma A/S vs. Isis Pharmaceuticals

Isis Pharmaceuticals filed a patent infringement lawsuit against Santaris Pharma A/S in the United States District Court of the Southern District of California in September 2011. Isis's infringement suit against Santaris is based upon Santaris's activities providing antisense drugs and antisense drug discovery services to several pharmaceutical companies.[26]